1. Field of the Invention
The present invention relates to immunoassays for topiramate and to topiramate analogs useful as immunogens and tracers and to anti-topiramate antibodies useful in the immunoassays.
2. Description of Related Art
Topiramate (2,3:4,5-bis-O-(1-methylethylidene)-.beta.-D-fructopyranose sulfamate) is a recently developed anti-epileptic drug which has been shown to be useful in the clinical treatment of convulsive disorders. Monitoring blood levels of therapeutic drugs is a routine practice to follow therapy and ensure safety in patients. Quantitation of drugs in tissues or body fluids is also important in pharmacokinetic studies and in monitoring patient compliance. Thus, there is a need for an analytical method to determine the concentration of topiramate in patient samples, particularly plasma and serum.
At present, there are two analytical methods available for measuring topiramate. Both utilize gas chromatography. The first employs gas chromatography coupled with flame ionization detection, the second, gas chromatography with mass spectroscopy. These methods are time consuming, require specialized equipment, highly trained analysts, and extensive sample preparation, and are expensive. The methods also require sample volumes that are too large to be used in pediatric testing unless topiramate concentrations are abnormally high. In short, the existing methods for topiramate are not suitable for routine use in a typical clinical chemistry lab or hospital lab.
Immunoassays have been used for over 20 years for monitoring serum or plasma levels of therapeutic drugs in the clinical laboratory and hospital. Some advantages of immunoassays are that such assays are accurate, sensitive, and in many commercial assay formats, easy to use. An immunoassay to measure topiramate would ensure the availability of an analytical method that could be used routinely to measure drug levels in patient samples. However, it can be difficult or impossible to construct a drug analog suitable for conjugation to a large molecule (such as a protein) to develop an immunogen that induces an antibody that reacts with the drug. Often, the derivatization necessary to create an immunogen sufficiently alters the drug such that the resulting antibodies recognize the analog, but not the drug. Therefore, preparation of analogs that are suitable for conjugation to a protein and induce antibodies that recognize both the analog and the drug is required to develop an immunoassay.